Tim-3 deteriorates neuroinflammatory and neurocyte apoptosis after subarachnoid hemorrhage through the Nrf2/HMGB1 signaling pathway in rats.
|
| Abstract |
Inflammation is known to play an important role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). T cell immunoglobulin and mucin domain-3 (Tim-3) has emerged as a critical regulator of adaptive and innate immune responses, and has been identified to play a vital role in certain inflammatory diseases; The present study explored the effect of Tim-3 on inflammatory responses and detailed mechanism in EBI following SAH. We investigated the effects of Tim-3 on SAH models established by endovascular puncture method in Sprague-Dawley rats. The present studies revealed that SAH induced a significant inflammatory response and significantly increased Tim-3 expression. Tim-3-AAV administration aggravated neurocyte apoptosis, brain edema, blood-brain barrier permeability, and neurological dysfunction; significantly inhibited Nrf2 expression; and increased HMGB1 expression and secretion of pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin (IL)-1 beta, IL-17, and IL-18. However, Tim-3 siRNA or NK252 administration abolished the pro-inflammatory effects of Tim-3. Our results indicate a function for Tim-3 as a molecular player that links neuroinflammation and brain damage after SAH. We reveal that Tim-3 overexpression deteriorates neuroinflammatory and neurocyte apoptosis after subarachnoid hemorrhage through the Nrf2/HMGB1 signaling pathway in rats.
|
|---|---|
| Authors | Shenquan Guo, Yuanzhi Li, Boyang Wei, Wenchao Liu, Ran Li, Wenping Cheng, Xin Zhang, Xuying He, Xifeng Li, Chuanzhi Duan |
| Journal | Aging (Aging (Albany NY)) Vol. 12 Issue 21 Pg. 21161-21185 (11 07 2020) ISSN: 1945-4589 [Electronic] United States |
| PMID | 33168786 (Publication Type: Journal Article) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!